Wild Blueberries in Colitis

Background: Chronic inflammatory bowel disease (IBD) affects the lives of millions of people worldwide due to recurrent, severe clinical symptoms, potential complications and ongoing medical interventions. The scientific community currently assumes a multicausal pathogenesis in IBD caused by an unfavorable constellation of genetic predisposition, imbalance of pathogenic to symbiotic gut bacteria (dysbiosis) and harmful environmental and lifestyle factors resulting in an excessive immune response. The intestinal barrier and the microbiome play a key role in maintaining intestinal balance and health. The intestinal barrier protects our body from bacteria, viruses and fungi in the intestinal lumen, while it enables the absorption of nutrients at the same time. In case of a leaky gut, microbial pathogens or their components can enter the deeper cell layers of the intestine and cause acute and long-term inflammatory reactions. The composition of the gut microbiome, i.e. the community of billions of microorganisms living in the gut, has a significant influence on the intestinal barrier and gut health. Beneficial bacteria stabilize the intestinal barrier, strengthen local defenses (mucin and IgA production) and inhibit pro-inflammatory immune reactions and cell death. In contrast, harmful bacteria (pathobionts) disrupt the intestinal barrier, dysregulate cell death and proliferation, which leads to the release of pro-inflammatory signaling substancesand and an immune response causing inflammation. While previous attempts to develop pharmacological therapies to improve gut barrier function have been unsuccessful, an increasing number of preclinical and clinical trial results highlight the significant impact of a plant-based diet through its modulatory effect on the gut microbiome and the gut barrier in IBD. However, further research is needed to evaluate the role of individual dietary components and complex dietary interventions with anti-inflammatory potential in the prevention and treatment of IBD. The high levels of prebiotic food components in a plant-rich diet are of particular importance in the treatment of intestinal barrier disorders and the microbiome. Preclinical and clinical studies highlight the modulatory effect of berries, especially blueberries (Vaccinium myrtillus), on the microbiome, gut health and inflammation due to their richness in prebiotically active polyphenols, flavonoids, anthocyanins and fiber. However, the influence of blueberries on the intestinal barrier and the microbiome in colitis patients has not yet been investigated. Mechanistically oriented clinical studies are needed to confirm the prebiotic and preclinical findings in the clinic. Through a targeted combination of clinical testing on patients, ex vivo examination of biopsy material and cell biological studies at protein and transcriptome level, it should be possible to develop a comprehensive picture of the influence of a blueberry-rich diet, but also of the underlying pathomechanisms affected. Aim of the study: Determination of the influence of a three-month blueberry-rich diet compared to a diet with a low blueberry content on disease activity, intestinal inflammation and symptoms in patients with chronic colitis - initiated as part of a routine inpatient stay during which patients are treated with a comprehensive multimodal integrative therapy concept with dietary changes. Exploratory study design: This is an exploratory, prospective, monocentric, randomized, crossover study. 60 IBD patients are randomized into two groups of 30 subjects each. During a period of 6 months, which follows the inpatient-initiated integrative medical lifestyle modification program, participants undergo two consecutive phases of 3 months each marked by a blueberry-rich and a blueberry-poor diet. Dependent on the study group, half of the study participants start the supplementary blueberry intake directly after the inpatient stay, the second half three months later (cross-over principle). Before the start of the study (W0), the colon of the participants is initially examined for macroscopic inflammation and for intestinal barrier disorders using confocal laser endomicroscopy as part of regular inpatient care. In order to investigate the influence of the integrative therapy with or without blueberry intake on the intestinal barrier and colonic inflammation, this will be checked after the end of the first 3 months (W12) and after 6 months (W24) in a voluntary control sigmoidoscopy with confocal laser endomicroscopy (CLE) as part of a short inpatient stay. During the endoscopy, biopsies, bile, stool, urine and blood samples important for the study are taken for examination. These serve to clarify mechanistic relationships between the intestinal barrier function, the microbiome, its metabolic products (metabolome), the immune system, the oxidative stress profile, the antioxidative capacity and the inflammatory process (inflammation markers, immune cells and cytokines). In addition, participants will receive questionnaires at all three time points (W0, W12, W24) to evaluate their IBD-specific and general quality of life, symptoms, disease activity, fatigue and stress levels.